Nature Microbiology最新文献_第3页

A broadly protective human antibody for GI genogroup noroviruses 一种针对消化道基因组诺罗病毒的广泛保护性人类抗体

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-10 DOI: 10.1038/s41564-025-01952-6

Inga Rimkute, Adam S. Olia, Mehin Suleiman, Kamron D. Woods, Tatsiana Bylund, Nicholas C. Morano, Ena S. Tully, Raffaello Verardi, Saran Bao, Margaret H. Beddall, Natthawan Chaimongkol, Mitzi M. Donaldson, Renguang Du, Caitlyn N. M. Dulan, Jason Gorman, Amy R. Henry, Chaim A. Schramm, Stanislav V. Sosnovtsev, Tyler Stephens, John-Paul Todd, Yaroslav Tsybovsky, Daniel C. Douek, Kim Y. Green, Reda Rawi, Lawrence Shapiro, Tongqing Zhou, Peter D. Kwong, Mario Roederer

{"title":"A broadly protective human antibody for GI genogroup noroviruses","authors":"Inga Rimkute, Adam S. Olia, Mehin Suleiman, Kamron D. Woods, Tatsiana Bylund, Nicholas C. Morano, Ena S. Tully, Raffaello Verardi, Saran Bao, Margaret H. Beddall, Natthawan Chaimongkol, Mitzi M. Donaldson, Renguang Du, Caitlyn N. M. Dulan, Jason Gorman, Amy R. Henry, Chaim A. Schramm, Stanislav V. Sosnovtsev, Tyler Stephens, John-Paul Todd, Yaroslav Tsybovsky, Daniel C. Douek, Kim Y. Green, Reda Rawi, Lawrence Shapiro, Tongqing Zhou, Peter D. Kwong, Mario Roederer","doi":"10.1038/s41564-025-01952-6","DOIUrl":"https://doi.org/10.1038/s41564-025-01952-6","url":null,"abstract":"Noroviruses infect millions each year, and while effective countermeasures are eagerly sought, none have been reported for the GI genogroup, first described more than 50 years ago. Here, to provide insight into GI norovirus neutralization, we isolated a broad GI antibody, 16E10, from a human blood donor and showed it neutralizes noroviruses in human enteroid cultures and abrogates or reduces infection in rhesus macaques. The cryogenic electron microscopy reconstruction of 16E10 with a norovirus protruding-domain dimer at 2.56-Å resolution reveals an exceptionally large binding surface, overlapping an antibody supersite, distal from host receptor-binding or cofactor-binding sites. Cryogenic electron microscopy reconstructions with virus-like particles (VLPs) showed that 16E10 disrupts protruding domains on the VLP surface and disassembles VLPs, altering viral organization required for avidity. While its epitope was generally conserved, 16E10 recognized multiple sequence-divergent residues, binding to which was enabled by corresponding cavities in the 16E10–norovirus interface. Broad recognition of noroviruses can thus incorporate sequence-divergent residues, through a cavity-based mechanism of diversity tolerance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"30 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Combining antibiotics to tackle antimicrobial resistance 作者更正：联合使用抗生素解决抗菌素耐药性问题

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-09 DOI: 10.1038/s41564-025-02003-w

William Hope, Sumathi Nambiar, Seamus O’Brien, Michael Sharland, David L. Paterson, Mo Yin, Ian H. Gilbert, Michael Ferguson, Sharon J. Peacock, Iain Buchan, Nada Reza, Vineet Dubey, Christopher A. Darlow, Alessandro Gerada, Alex Howard

引用次数: 0

Integrating microbial GWAS and single-cell transcriptomics reveals associations between host cell populations and the gut microbiome 整合微生物GWAS和单细胞转录组学揭示了宿主细胞群和肠道微生物组之间的关联

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-07 DOI: 10.1038/s41564-025-01978-w

Jingjing Li, Yunlong Ma, Yue Cao, Gongwei Zheng, Qing Ren, Cheng Chen, Qunyan Zhu, Yijun Zhou, Yu Lu, Yaru Zhang, Chunyu Deng, Wei-Hua Chen, Jianzhong Su

{"title":"Integrating microbial GWAS and single-cell transcriptomics reveals associations between host cell populations and the gut microbiome","authors":"Jingjing Li, Yunlong Ma, Yue Cao, Gongwei Zheng, Qing Ren, Cheng Chen, Qunyan Zhu, Yijun Zhou, Yu Lu, Yaru Zhang, Chunyu Deng, Wei-Hua Chen, Jianzhong Su","doi":"10.1038/s41564-025-01978-w","DOIUrl":"https://doi.org/10.1038/s41564-025-01978-w","url":null,"abstract":"Microbial genome-wide association studies (GWAS) have uncovered numerous host genetic variants associated with gut microbiota. However, links between host genetics, the gut microbiome and specific cellular contexts remain unclear. Here we use a computational framework, scBPS (single-cell Bacteria Polygenic Score), to integrate existing microbial GWAS and single-cell RNA-sequencing profiles of 24 human organs, including the liver, pancreas, lung and intestine, to identify host tissues and cell types relevant to gut microbes. Analysing 207 microbial taxa and 254 host cell types, scBPS-inferred cellular enrichments confirmed known biology such as dominant communications between gut microbes and the digestive tissue module and liver epithelial cell compartment. scBPS also identified a robust association between Collinsella and the central-veinal hepatocyte subpopulation. We experimentally validated the causal effects of Collinsella on cholesterol metabolism in mice through single-nuclei RNA sequencing on liver tissue to identify relevant cell subpopulations. Mechanistically, oral gavage of Collinsella modulated cholesterol pathway gene expression in central-veinal hepatocytes. We further validated our approach using independent microbial GWAS data, alongside single-cell and bulk transcriptomic analyses, demonstrating its robustness and reproducibility. Together, scBPS enables a systematic mapping of the host–microbe crosstalk by linking cell populations to their interacting gut microbes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"108 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pseudomonas syringae subpopulations cooperate by coordinating flagellar and type III secretion spatiotemporal dynamics to facilitate plant infection 丁香假单胞菌亚群通过协调鞭毛和III型分泌的时空动态进行合作，促进植物侵染

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-04-02 DOI: 10.1038/s41564-025-01966-0

Nieves López-Pagán, José S. Rufián, Julien Luneau, María-Antonia Sánchez-Romero, Laurent Aussel, Simon van Vliet, Javier Ruiz-Albert, Carmen R. Beuzón

{"title":"Pseudomonas syringae subpopulations cooperate by coordinating flagellar and type III secretion spatiotemporal dynamics to facilitate plant infection","authors":"Nieves López-Pagán, José S. Rufián, Julien Luneau, María-Antonia Sánchez-Romero, Laurent Aussel, Simon van Vliet, Javier Ruiz-Albert, Carmen R. Beuzón","doi":"10.1038/s41564-025-01966-0","DOIUrl":"10.1038/s41564-025-01966-0","url":null,"abstract":"Isogenic bacterial populations can display probabilistic cell-to-cell variation in response to challenges. This phenotypic heterogeneity can affect virulence in animals, but its impact on plant pathogens is unknown. Previously, we showed that expression of the type III secretion system (T3SS) of the plant pathogen Pseudomonas syringae displays phenotypic variation in planta. Here we use flow cytometry and microscopy to investigate single-cell flagellar expression in relation to T3SS expression, showing that both systems undergo phenotypic heterogeneity in vitro in apoplast-mimicking medium and within apoplastic microcolonies throughout colonization of Phaseolus vulgaris. Stochastic, spatial and time factors shape the dynamics of a phenotypically diverse pathogen population that displays division of labour during colonization: effectors produced by T3SS-expressing bacteria act as ‘common goods’ to suppress immunity, allowing motile flagella-expressing bacteria to increase and leave infected tissue before necrosis. These results showcase the mechanisms of bacterial specialization during plant colonization in an environmentally and agriculturally relevant system. Single-cell gene expression analysis reveals phenotypic heterogeneity to enable bacterial specialization over the course of plant colonization.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"958-972"},"PeriodicalIF":20.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-025-01966-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Profiling Salmonella transcriptional dynamics during macrophage infection using a comprehensive reporter library 利用综合报告文库分析巨噬细胞感染期间沙门氏菌转录动力学

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-04-02 DOI: 10.1038/s41564-025-01953-5

Taylor H. Nguyen, Benjamin X. Wang, Oscar R. Diaz, Manohary Rajendram, Joy A. McKenna, Daniel S. C. Butler, Karsten Hokamp, Jay C. D. Hinton, Denise M. Monack, Kerwyn Casey Huang

{"title":"Profiling Salmonella transcriptional dynamics during macrophage infection using a comprehensive reporter library","authors":"Taylor H. Nguyen, Benjamin X. Wang, Oscar R. Diaz, Manohary Rajendram, Joy A. McKenna, Daniel S. C. Butler, Karsten Hokamp, Jay C. D. Hinton, Denise M. Monack, Kerwyn Casey Huang","doi":"10.1038/s41564-025-01953-5","DOIUrl":"10.1038/s41564-025-01953-5","url":null,"abstract":"Salmonella enterica serovar Typhimurium must adapt to rapid environmental shifts, including those encountered upon entry and during replication to survive within macrophages during pathogenesis. Despite extensive RNA-seq-based investigations, questions remain regarding the range, timing and magnitude of response dynamics. Here we constructed a comprehensive GFP-reporter strain library representing 2,901 computationally identified Salmonella promoter regions to study time-resolved Salmonella transcriptional responses. Promoter activity was measured during in vitro growth and during intracellular infection of RAW 264.7 macrophages. Using bulk measurements and single-cell imaging, we uncovered condition-specific transcriptional regulation and population-level heterogeneity in SPI2-related promoter activity. We also discovered previously unidentified transcriptional activity from 234 promoters. These analyses revealed metabolic shifts including requirements for mntS expression to support manganese homeostasis and expression of Entner–Doudoroff pathway-associated genes to support growth within macrophages. Our library and datasets, made available through the online tool SalComKinetics, provide resources for systems-level interrogation of Salmonella transcriptional dynamics. Construction and analysis of 2,901 promoter–GFP fusions in Salmonella reveal dynamic, heterogeneous transcriptional activity, including roles for manganese homeostasis and Entner–Doudoroff carbon metabolism in promoting intramacrophage growth and survival of bacteria.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"1006-1023"},"PeriodicalIF":20.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circadian rhythms mediate malaria transmission 昼夜节律调节疟疾传播

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-04-02 DOI: 10.1038/s41564-025-01950-8

引用次数: 0

A quinolone N-oxide antibiotic selectively targets Neisseria gonorrhoeae via its toxin–antitoxin system 一种喹诺酮类n -氧化物抗生素通过其毒素-抗毒素系统选择性靶向淋病奈瑟菌

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-04-02 DOI: 10.1038/s41564-025-01968-y

Ann-Kathrin Mix, Thi Hong Nhung Nguyen, Tamara Schuhmacher, Dávid Szamosvári, Petra Muenzner, Paula Haas, Lydia Heeb, Haleluya T. Wami, Ulrich Dobrindt, Yasar Özge Delikkafa, Thomas U. Mayer, Thomas Böttcher, Christof R. Hauck

{"title":"A quinolone N-oxide antibiotic selectively targets Neisseria gonorrhoeae via its toxin–antitoxin system","authors":"Ann-Kathrin Mix, Thi Hong Nhung Nguyen, Tamara Schuhmacher, Dávid Szamosvári, Petra Muenzner, Paula Haas, Lydia Heeb, Haleluya T. Wami, Ulrich Dobrindt, Yasar Özge Delikkafa, Thomas U. Mayer, Thomas Böttcher, Christof R. Hauck","doi":"10.1038/s41564-025-01968-y","DOIUrl":"10.1038/s41564-025-01968-y","url":null,"abstract":"Gonorrhoea is a major sexually transmitted infection and the emergence of multidrug-resistant Neisseria gonorrhoeae poses a global health threat. To identify candidate antibiotics against N. gonorrhoeae, we screened Pseudomonas aeruginosa-derived secondary metabolites and found that 2-nonyl-4-quinolone N-oxide (NQNO) abrogated growth of N. gonorrhoeae in vitro. NQNO did not impair growth of commensal Neisseriae, vaginal lactobacilli or viability of human cells. Mechanistically, NQNO disrupted the electron transport chain, depleted ATP and NADH levels and increased oxidative stress. This triggered activation of a toxin–antitoxin system, release of the endogenous Zeta1 toxin and bacterial death. In a mouse model of infection, topical application of NQNO prevented colonization by N. gonorrhoeae. Chemical modification yielded 3-methyl NQNO, which exhibited nanomolar potency against multidrug-resistant strains, lack of resistance development and significantly reduced pathogen numbers during experimental infection of mice. These findings show the potential for selective killing of bacterial pathogens such as multidrug-resistant N. gonorrrhoeae through activation of endogenous toxins. Pseudomonas aeruginosa-derived 2-nonyl-4-quinolone N-oxide exerts bactericidal effects on Neisseria gonorrhoea via zeta1–epsilon1 toxin–antitoxin activation in vitro and abrogates experimental infection in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"939-957"},"PeriodicalIF":20.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-025-01968-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Model behaviour 模型行为

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-04-02 DOI: 10.1038/s41564-025-01987-9

引用次数: 0

The challenges of treating severe A(H5N1) influenza 治疗严重甲型H5N1流感的挑战

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-04-02 DOI: 10.1038/s41564-025-01974-0

引用次数: 0

Colonic goblet cell-associated antigen passages mediate physiologic and beneficial translocation of live gut bacteria in preweaning mice 结肠杯状细胞相关抗原传代介导断奶前小鼠活肠道细菌的生理和有益易位

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-04-01 DOI: 10.1038/s41564-025-01965-1

Sreeram Udayan, Alexandria N. Floyd, Vini John, Bibiana E. Barrios, Brigida A. Rusconi, Keely G. McDonald, Ellen Merrick Schill, Devesha H. Kulkarni, Andrew L. Martin, Rafael Gutierrez, Khushi B. Talati, Dalia L. Harris, Sushma Sundas, Kayla M. Burgess, Jocelyn T. Pauta, Elisabeth L. Joyce, Jacqueline D. Wang, Leslie D. Wilson, Kathryn A. Knoop, Phillip I. Tarr, Chyi-Song Hsieh, Rodney D. Newberry

{"title":"Colonic goblet cell-associated antigen passages mediate physiologic and beneficial translocation of live gut bacteria in preweaning mice","authors":"Sreeram Udayan, Alexandria N. Floyd, Vini John, Bibiana E. Barrios, Brigida A. Rusconi, Keely G. McDonald, Ellen Merrick Schill, Devesha H. Kulkarni, Andrew L. Martin, Rafael Gutierrez, Khushi B. Talati, Dalia L. Harris, Sushma Sundas, Kayla M. Burgess, Jocelyn T. Pauta, Elisabeth L. Joyce, Jacqueline D. Wang, Leslie D. Wilson, Kathryn A. Knoop, Phillip I. Tarr, Chyi-Song Hsieh, Rodney D. Newberry","doi":"10.1038/s41564-025-01965-1","DOIUrl":"10.1038/s41564-025-01965-1","url":null,"abstract":"Gut-resident microorganisms have time-limited effects in distant tissues during early life. However, the reasons behind this phenomenon are largely unknown. Here, using bacterial culture techniques, we show that a subset of live gut-resident bacteria translocate and disseminate to extraintestinal tissues (mesenteric lymph nodes and spleen) in preweaning (day of life 17), but not adult (day of life 35), mice. Translocation and dissemination in preweaning mice appeared physiologic as it did not induce an inflammatory response and required host goblet cells, the formation of goblet cell-associated antigen passages, sphingosine-1-phosphate receptor-dependent leukocyte trafficking and phagocytic cells. One translocating strain, Lactobacillus animalisWU, showed antimicrobial activity against the late-onset sepsis pathogen Escherichia coli ST69 in vitro, and its translocation was associated with protection from systemic sepsis in vivo. While limited in context, these findings challenge the idea that translocation of gut microbiota is pathological and show physiologic and beneficial translocation during early life. Colonic goblet cell-associated passages allow translocation of live bacteria to other organs in early life, potentially leading to beneficial impacts.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"927-938"},"PeriodicalIF":20.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0